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In vitro cytotoxicity and antiviral efficacy against feline herpesvirus type 1 of famciclovir and its metabolites

Authors

  • Allyson D. Groth,

    1. Veterinary Medical Teaching Hospital, University of California, Davis, Davis, CA, USA
    Current affiliation:
    1. Small Animal Specialist Hospital, North Ryde, NSW, Australia
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  • Marcos T. Contreras,

    1. Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA
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  • Helen K. Kado-Fong,

    1. Department of Surgical and Radiological Sciences, University of California, Davis, Davis, CA, USA
    Current affiliation:
    1. California Animal Health & Food Safety Laboratory System, University of California, Davis, Davis, CA, USA
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  • Kyvan Q. Nguyen,

    1. Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA
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  • Sara M. Thomasy,

    1. Veterinary Medical Teaching Hospital, University of California, Davis, Davis, CA, USA
    Current affiliation:
    1. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA
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  • David J. Maggs

    Corresponding author
    1. Department of Surgical and Radiological Sciences, University of California, Davis, Davis, CA, USA
    • Address communications to:

      Dr. D. J. Maggs

      Tel.: (530) 752 1393

      Fax: (530) 752 6042

      e-mail: djmaggs@ucdavis.edu

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Abstract

Objectives

To assess in vitro the antiviral efficacy against feline herpesvirus (FHV-1) and cytotoxicity for cultured feline cells of famciclovir and its metabolites, BRL 42359 and penciclovir. To investigate the effect of timing of penciclovir application on in vitro antiviral activity.

Procedures

Plaque reduction assays were used to estimate antiviral efficacy of all compounds and the effect of penciclovir exposure before or after exposure to a FHV-1 field isolate. Cytotoxicity was evaluated by assessing cell morphology and viable cell number for 72 h following exposure to each compound.

Results

The penciclovir concentration that inhibited FHV-1-induced plaque formation by 50% (IC50) was 0.86 μg/mL (3.4 μm). Famciclovir and BRL 42359 had no antiviral effect against FHV-1 at any concentration assessed. Antiviral activity was significantly enhanced when cells were exposed to 4 μm penciclovir (approximate IC50) for 1 h but not for 24 h before viral adsorption. Delaying exposure of cells to penciclovir for 1, 2, or 4 h after viral adsorption significantly enhanced antiviral activity. Relative to untreated control wells, >88% of cells remained viable when exposed to famciclovir (100 μm), BRL 42359 (1.06 mm), or penciclovir (40 μm) for 72 h. No morphologic evidence of cytotoxicity was noted.

Conclusions

Penciclovir demonstrates potent antiviral activity against FHV-1 and may be effective at lower tissue, tear, and plasma concentrations than previously targeted. The duration of in vitro antiviral effect of penciclovir suggests that frequent famciclovir administration may be necessary in vivo. Famciclovir and BRL 42359 showed no signs of in vitro cytotoxicity.

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